title: LPS sensitizes TRPV1 via activation of TLR4 in trigeminal sensory neurons.
abstract: Recent studies have demonstrated that the lipopolysaccharide (LPS) receptor (TLR4) is expressed in TRPV1 containing trigeminal sensory neurons. In this study, we evaluated whether LPS activates trigeminal neurons, and sensitizes TRPV1 responses via TLR4. To test this novel hypothesis, we first demonstrated that LPS binds to receptors in trigeminal neurons using competitive binding. Second, we demonstrated that LPS evoked a concentration-dependent increase in intracellular calcium accumulation (Ca(2+))(i) and inward currents. Third, LPS significantly sensitized TRPV1 to capsaicin measured by (Ca(2+))(i), release of calcitonin gene-related peptide, and inward currents. Importantly, a selective TLR4 antagonist blocked these effects. Analysis of these data, collectively, demonstrates that LPS is capable of directly activating trigeminal neurons, and sensitizing TRPV1 via a TLR4-mediated mechanism. These findings are consistent with the hypothesis that trigeminal neurons are capable of detecting pathogenic bacterial components leading to sensitization of TRPV1, possibly contributing to the inflammatory pain often observed in bacterial infections.
authors.affiliation: Department of Endodontics, University of Texas Health Science Center at San Antonio, Mail Code 7892, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. Diogenes@uthscsa.edu
authors.forename: A
authors.initials: A
authors.lastname: Diogenes
authors.forename: C C R
authors.initials: CC
authors.lastname: Ferraz
authors.forename: A N
authors.initials: AN
authors.lastname: Akopian
authors.forename: M A
authors.initials: MA
authors.lastname: Henry
authors.forename: K M
authors.initials: KM
authors.lastname: Hargreaves
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis; D020013:Calcium Signaling; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D008070:Lipopolysaccharides / Q000378:metabolism*; D008297:Male; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000166:cytology / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D018689:Sensory System Agents; D050916:TRPV Cation Channels; D051197:Toll-Like Receptor 4; C493922:Trpv1 protein, rat; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin